Basic Biologic Interactions of Radiation

IONIZATION

RADIOLYSIS OF WATERBecause the human body is an aqueous solution that contains approximately 80% water molecules, irradiation of water represents the principal radiation interaction in the body. When water is irradiated, it dissociates into other molecular products; this action is called radiolysis of water

When an atom of water (H2O) is irradiated, it is ionized and dissociates into two ions—an ion pair

IONIZATION

The HOH and HOH− ions are relatively unstable and can dissociate into still smaller molecules

The final result of the radiolysis of water is the formation of an ion pair, H+ and OH−, and two free radicals, H* and OH*. The ions can recombine; therefore, no biologic damage would occur

These types of ions are not unusual. Many molecules in aqueous solution exist in a loosely ionized state because of their structure. Salt (NaCl), for instance, easily dissociates into Na+ and Cl− ions. Even in the absence of radiation, water can dissociate into H+ and OH− ions.

A free radical is an uncharged molecule that contains a single unpaired electron in the outer shell.

Free radicals are unstable and therefore exist with a lifetime of less than 1 ms. During that time, however, they are capable of diffusion through the cell and interaction at a distant site. Free radicals contain excess energy that can be transferred to other molecules to disrupt bonds and produce point lesions at some distance from the initial ionizing event

The H* and OH* molecules are not the only free radicals that are produced during the radiolysis of water. The OH* free radical can join with a similar molecule to form hydrogen peroxide

Hydrogen peroxide is poisonous to the cell and therefore acts as a toxic agent.

The H* free radical can interact with molecular oxygen to form the hydroperoxyl radical

The hydroperoxyl radical, along with hydrogen peroxide, is considered to be the principal damaging product after the radiolysis of water. Hydrogen peroxide also can be formed by the interaction of two hydroperoxyl radicals

Some organic molecules, symbolized as RH, can become reactive free radicals

When oxygen is present, yet another species of free radical is possible

Free radicals are energetic molecules because of their unique structure. This excess energy can be transferred to DNA, and this can result in bond breaks.

When biologic material is irradiated in vivo, the harmful effects of irradiation occur because of damage to a particularly sensitive molecule, such as DNA. Evidence for the direct effect of radiation comes from in vitro experiments wherein various molecules can be irradiated in solution. The effect is produced by ionization of the target molecule

If the initial ionizing event occurs on the target molecule, the effect of radiation is direct

On the other hand, if the initial ionizing event occurs on a distant, noncritical molecule, which then transfers the energy of ionization to the target molecule, indirect effect has occurred. Free radicals, with their excess energy of reaction, are the intermediate molecules. They migrate to the target molecule and transfer their energy, which results in damage to that target molecule.

The principal effect of radiation on humans is indirect

It is not possible to identify whether a given interaction with the target molecule resulted from direct or indirect effect. However, because the human body consists of approximately 80% water and less than 1% DNA, it is concluded that essentially all of the effects of irradiation in vivo result from indirect effect. When oxygen is present, as in living tissue, the indirect effects are amplified because of the additional types of free radicals that are formed

When one irradiates tissue, the response of the tissue is determined principally by the amount of energy deposited per unit mass—the dose in rad (Gyt). Even under controlled experimental conditions, however, when equal doses are delivered to equal specimens, the response may not be the same because of other modifying factors. A number of physical factors affect the degree of radiation response

Linear energy transfer (LET) is a measure of the rate at which energy is transferred from ionizing radiation to soft tissue. It is another method of expressing radiation quality and determining the value of the radiation weighting factor (WR) used in radiation protection . LET is expressed in units of kiloelectron volt of energy transferred per micrometer of track length in soft tissue (keV/μm).

The ability of ionizing radiation to produce a biologic response increases as the LET of radiation increases. When LET is high, ionizations occur frequently, increasing the probability of interaction with the target molecule.

As the LET of radiation increases, the ability to produce biologic damage also increases. This relative effect is quantitatively described by the relative biologic effectiveness (RBE).

The standard radiation, by convention, is orthovoltage x-radiation in the range of 200 to 250 kVp. This type of x-ray beam was used for many years in radiation oncology and in essentially all early radiobiologic research.Diagnostic x-rays have an RBE of 1. Radiations with lower LET than diagnostic x-rays have an RBE less than 1, whereas radiations with higher LET have a higher RBE.

Type of Radiation LET (keV/μm) RBE

25 MV x-rays 0.2 0.8

60Co gamma rays 0.3 0.9

1 MeV electrons 0.3 0.9

Diagnostic x-rays 3.0 1.0

10 MeV protons 4.0 5.0

Fast neutrons 50.0 10

5 MeV alpha particles

100.0 20

Heavy nuclei 1000.0 30

Question: When mice are irradiated with 250 kVp x-rays, death occurs at 650 rad (6.5 Gyt). If similar mice are irradiated with fast neutrons, death occurs at only 210 rad (2.1 Gyt). What is the RBE for the fast neutrons?

If a dose of radiation is delivered over a long period of time rather than quickly, the effect of that dose is lessened. Stated differently, if the time of irradiation is lengthened, a higher dose is required to produce the same effect. This lengthening of time can be accomplished in two ways.If the dose is delivered continuously but at a lower dose rate, it is said to be protracted. Six hundred rad (6 Gyt) delivered in 3 min (200 rad/min [2 Gyt/min]) is lethal for a mouse. However, when 600 rad is delivered at the rate of 1 rad/hr (10 mGyt/hr) for a total time of 600 hr, the mouse will survive

If the 600 rad dose is delivered at the same dose rate, 200 rad/min, but in 12 equal fractions of 50 rad (500 mGyt), all separated by 24 hr, the mouse will survive. In this situation, the dose is said to be fractionated

Dose protraction and fractionation cause less effect because time is allowed for intracellular repair and tissue recovery.